Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Amonafide in Treating Women With Metastatic Breast Cancer That Has Progressed After Previous Chemotherapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Over 18	NCI, Pharmaceutical / Industry	MSKCC-03080 XANTHUS-0001A1-200-GL, NCT00074100

Objectives

Primary

1. Determine the time to progression in women with metastatic breast cancer who have progressed after prior chemotherapy and are now treated with amonafide.
2. Determine the overall response rate (complete and partial response) in patients treated with this drug.
3. Determine the safety of a phenotypically driven dosing regimen of this drug in these patients.

Secondary

1. Determine the time to tumor response, duration of response, and time to treatment failure in patients treated with this drug.
2. Determine the overall survival of patients treated with this drug.
3. Determine the pharmacokinetic profile of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Metastatic (stage IV) disease



• Relapsed after 1 of the following prior therapy regimens*:
  • Adjuvant therapy containing an anthracycline and a taxane
  • Adjuvant anthracycline therapy followed by first-line metastatic treatment containing a taxane

   [Note: *No relapse within 12 months of initiation of prior therapy]




• Measurable disease by CT scan or MRI
  • No ascites, pleural effusions, or osteoblastic bone metastases as the only site of measurable disease



• Refractory to hormonal anticancer therapy completed more than 4 weeks before study therapy



• HER2/neu positive allowed provided patient received prior trastuzumab (Herceptin®)
  • MUGA or echocardiogram normal while on trastuzumab



• No known history of or current brain or leptomeningeal metastases



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• More than 3 months since prior trastuzumab
• More than 2 weeks since prior growth factor therapy (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF])
• No concurrent systemic anticancer immune modulators

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics
• More than 4 weeks since prior hormonal therapy
• No concurrent anticancer hormonal therapy
• No concurrent chronic systemic steroids
  • Concurrent topical or inhaled steroids for dermatological or allergy/asthma conditions allowed provided therapy was initiated prior to study enrollment
• Concurrent hormone replacement therapy allowed provided therapy was initiated prior to study enrollment

Radiotherapy

• More than 30 days since prior radiotherapy
• No concurrent radiotherapy directed at target lesions

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• More than 30 days since prior investigational new drug
• More than 2 weeks since prior blood transfusion
• No other concurrent systemic anticancer agents, including immunosuppressive agents
• No other concurrent investigational agents
• Concurrent bisphosphonates allowed provided therapy was initiated prior to study enrollment

Patient Characteristics:

Age

• Over 18

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• WBC at least 3,000/mm³
• Neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10.0 g/dL
• No clinically significant abnormal hematological parameters

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN in case of liver metastases)
• AST or ALT no greater than 2.5 times ULN (5 times ULN in case of liver metastases)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• See Disease Characteristics
• No myocardial infarction within the past 3 months
• No unstable angina pectoris
• No New York Heart Association class III or IV heart disease
• No uncontrolled arrhythmia
• No cardiac insufficiency
• No uncontrolled hypertension
• LVEF at least 50% OR at least lower limit of normal

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception 4 weeks before, during, and for at least 4 weeks after study participation
• No preexisting neuropathy (motor or sensory) greater than grade 2
• No clinically significant abnormal biochemical parameters
• No clinically significant active infection
• No other prior malignancy except cured nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No other serious illness or medical condition
• No psychological illness or condition that would preclude study participation
• No other known condition that would preclude study participation

Expected Enrollment

A total of 175 patients will be accrued for this study within 1 year.

Outline

This is an open-label, multicenter study.

Patients receive amonafide IV over 1 hour on days 1-5. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional courses (beyond 5 courses) at the investigator's discretion.

Patients are followed at 30 days and then every 3 months.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Clifford Hudis, MD, Principal investigator		Ph: 646-888-4551; 800-525-2225

Registry Information
Official Title		Amonafide: Individual Phenotype-Adjusted Chemotherapy for Women with Metastatic Breast Cancer Who Have Progressed Despite Prior Chemotherapy
Trial Start Date		2003-08-12
Registered in ClinicalTrials.gov		NCT00074100
Date Submitted to PDQ		2003-10-22
Information Last Verified		2004-08-11
NCI Grant/Contract Number		P30-CA08748

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